Kuse Yoshiki, Tsuruma Kazuhiro, Kanno Yusuke, Shimazawa Masamitsu, Hara Hideaki
Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical UniversityGifu, Japan.
Front Pharmacol. 2017 Apr 18;8:207. doi: 10.3389/fphar.2017.00207. eCollection 2017.
The C-C chemokine receptor type 3 (CCR3) is the receptor for eotaxins (CCL-11, 24, 26), RANTES (CCL-5) and MCP-3 (CCL-7). It was reported that an inhibition of CCR3 by antagonists or antibodies reduces the degree of laser-induced choroidal neovascularization in mice, a model for wet age-related macular degeneration (AMD). Although several chemokine receptors have the potential of reducing the degree of the chronic inflammation in experimental dry AMD, the association of CCR3 remains unknown. The purpose of this study was to determine the role played by CCR3 in the death of 661W cells which are cells of a murine photoreceptor-derived cell line as an model of dry AMD. The expression of CCR3 was increased in the 661W cells after light exposure. Inhibition of CCR3 reduced the rate of cell death induced by light exposure. A blockade of CCR3 signaling by CCR3 silencing and two kinds of CCR3 antagonists, SB 328437 and SB 297006, reduced the rate of light-induced cell death. In addition, CCR3 inhibition decreased the level of reactive oxygen species and the activation of caspase-3/7 induced by light exposure. These findings indicated that the CCR3 blockade should be considered for the treatment of the dry AMD.
C-C趋化因子受体3（CCR3）是嗜酸性粒细胞趋化因子（CCL-11、24、26）、RANTES（CCL-5）和MCP-3（CCL-7）的受体。据报道，在湿性年龄相关性黄斑变性（AMD）模型小鼠中，拮抗剂或抗体对CCR3的抑制作用可降低激光诱导的脉络膜新生血管形成程度。尽管几种趋化因子受体有降低实验性干性AMD慢性炎症程度的潜力，但CCR3与之的关联仍不清楚。本研究的目的是确定CCR3在作为干性AMD模型的小鼠光感受器来源细胞系661W细胞死亡中所起的作用。光照后661W细胞中CCR3的表达增加。抑制CCR3可降低光照诱导的细胞死亡率。通过CCR3沉默以及两种CCR3拮抗剂SB 328437和SB 297006阻断CCR3信号传导，可降低光照诱导的细胞死亡率。此外，抑制CCR3可降低光照诱导的活性氧水平以及caspase-3/7的激活。这些发现表明，在干性AMD的治疗中应考虑阻断CCR3。
